Angioplasty is a safe and effective way to unblock coronary arteries. In a typical procedure, a catheter is inserted into the groin or arm of a subject and guided forward through the aorta and into the coronary arteries of the heart. There, blocked arteries can be opened with a balloon positioned at the tip of the catheter. Initially, angioplasty was performed only with balloon catheters, but technical advances have been made and improved patient outcome has been achieved with the placement of small metallic spring-like devices called “stents” at the site of the blockage. The implanted stent serves as a scaffold that keeps the artery open. Angioplasty and stenting techniques are widely used around the world and provide an alternative option to bypass surgery for improving blood flow to the heart muscle. There are, however, limitations associated with angioplasty and stenting, one of which is called “restenosis.”
Restenosis occurs when the treated vessel becomes blocked again. For example, when a stent is placed in a blood vessel, new tissue grows inside the stent, covering the struts of the stent. Initially, this new tissue consists of healthy cells from the lining of the arterial wall (i.e., endothelium). This is a favorable effect because development of normal lining over the stent allows blood to flow smoothly over the stented area without clotting. Later, scar tissue may form underneath the new healthy lining. However, in about 25% of patients, the growth of scar tissue underneath the lining of the artery may be so thick that it can obstruct the blood flow and produce another blockage. “In-stent” restenosis is typically seen 3 to 6 months after the initial procedure. Another significant limitation of the use of stents is stent thrombosis, which, although rare (occurring in only 1% of patients), most commonly presents as acute myocardial infarction.
If restenosis occurs following balloon angioplasty, it is generally referred to as post-angioplasty restenosis or PARS. Typically, the angioplasty balloon is inserted into the vessel and its inflation physically compresses the occlusion against the artery walls, thus widening the size of the lumen and increasing blood flow. However this action can damage the vessel walls, which can cause a reactionary physiological response that can include the formation of a thrombosis immediately after the trauma, followed by an inflammatory immune response occurring 3-6 months after the initial procedure. The inflammatory response is typically accompanied by cellular proliferation in the vessel walls; this cellular proliferation can lead to restenosis. In cardiac procedures, balloon angioplasty has been associated with a high incidence of restenosis, with rates ranging from 25% to 50%, and the majority of these patients need further angioplasty within 6 months. In peripheral procedures, restenosis rates can be as high as 35%.
To combat restenosis, drug-eluding stents (DES) were developed. DES slowly release a drug that blocks cell proliferation and reduce the rates of restenosis to less than 10%. However, DES have led to new complications including, late and very late stent thrombosis as a result of delayed healing, local inflammation, and impaired endothelial function. These limitations of DES prompted a search for improved solutions for treating restenosis, such as the local delivery of drugs via non-stent platforms, including drug-eluting balloons (DEB).